Rapid diagnostic tests (RDTs) play an important and growing role in the continuum of care worldwide. Administered either at the point of care in doctors' offices, hospitals, urban and remote clinics, or by ambulatory health workers and providing immediate results these tests contribute to improved access, lower cost, and better-quality healthcare. An increasing number of RDTs are available for home use by patients and the general public for testing of acute and chronic conditions. The dominant technology used for RDTs is Lateral Flow Immuno-Chromatographic assay (LFI) and with the worldwide annual value of LFI tests and services of $18B according to BCC Research. RDTs are also available in other variations of immunoassays, such as fluorescent LFIs, flow-through, and dipstick tests. In fact, contemplated embodiments described here are applicable to any RDT using a change of the optical properties as the mechanism of action.
As valuable as RDTs are, they can be less reliable and accurate, because they are typically read visually, and therefore, are subject to human error [1-19]. These inherent errors can be substantially alleviated through the use of electronic readers originally developed by ESE GmBH and today available from a number of sources [21, 22]. They are typically desktop instruments for laboratory use, can be rather large and heavy and can cost thousands of dollars. Recently, significant progress in the state-of-the-art technology was achieved by Professor Aydogan Ozcan and his research group at UCLA using a smartphone as the technology platform. In addition, they developed a reader [17, 20] (hereafter Mudanyali reader) with the following advantages: a) small, handheld and light (˜2.3 oz), b) sensitive and accurate with transmission or reflection readout mode, c) impervious to ambient lighting conditions, d) automated test readout with electronic data capture and telemetry using smartphone communication capabilities, e) centralized data collection with geomapping capabilities and interfaces to health information systems, and f) low cost achieved by piggybacking on the enormous production volume of smartphones.
Despite the advantages, there are opportunities available for these conventional readers to be improved. For instance, conventional systems achieve low cost by using a smartphone which is inserted into a reader body that provides RDT illumination, ambient isolation, and cassette housing. However, different models of smartphones from a single manufacturer or even more from a variety of vendors all have different mechanical dimensions, and they wouldn't fit into a body designed for one specific smartphone model. This precludes users from using their own smartphone for the reader: they have to buy another dedicated smartphone which is a significant cost increase, not to mention adding to the number of devices that need to be stored and utilized.
Readers require sources of illumination and associated control electronics and at least one battery housed outside the smartphone. In Mudanyali's conventional reader, the control is provided by the software application in the smartphone via a physical cable, which plugs into the smartphone micro USB power connector. External cabling adds to the cost and reduces reliability; besides, many smartphones do not have the capability for outbound control through their power connector. Also, the reference that discloses the Mudanyali reader describes a power source disposed in the attachment, such that the self-powered reader can be controlled via a physical button located on the attachment. This operation fully depends on operator's ability to use the reader and increases the complexity of operation. It would be ideal if contemplated readers and systems corrected many of the before mentioned deficiencies of the prior art, such as by simplifying communications to and from the reader, minimizing or removing additional hardware or system requirements, providing a universal test tray, test port, or test insertion system, so that the reader and related system can be utilized for as many tests as possible without modification. It would also be ideal if contemplated readers were simplified altogether by removing the necessity for separate control by or use of a separate wireless device, such as a smartphone, tablet, or any other wirelessly-enabled device.
Moreover and more importantly with respect to contemplated embodiments herein, Mudanyali's reader is capable of accommodating different tests types using special customized-trays per cassette type, but these customized trays must be changed out for each type of test cassette used. Therefore, it doesn't provide a universal solution to image any test without additional mechanical components. This required customization can increase the initial expense of ownership and use, along with leading to a system that contains more “moving pieces” or components that need to be stored and utilized. A user must be able to know which customized tray to use and must properly store it, so that another user can find the customized tray and know how it should be used with respect to the individual test. A universal reader should be readily able to work with a significant number of different test cassettes without a need for any mechanical adaptation or additional mechanical components, unlike the ones described above.
Recently another implementation of a smartphone-based reader has been disclosed [23], which depends on the optimized Rayleigh/Mie scatter detection by taking into consideration the optical nitrocellulose membrane and gold nanoparticles on rapid tests. For each test type, this approach requires a complicated and precise calibration procedure to determine the optimum angles of illumination that minimize the Mie scattering from the membrane while maximizing the Rayleigh scatter detection from the gold nanoparticles on and inside the membrane. Because of the significant variation between different RDT types and also the variation within the samples of same RDT type in terms of use of components (e.g., membranes and nanoparticles) and position/orientation of membrane and cassettes, successful implementation of this concept on a portable unit is quite challenging and not feasible. For instance, the coefficient of variation (CV) exceeds 50% in some of their measurements on quantitative tests [23]. This reader variation is generally not acceptable even in qualitative measurements. This alignment-dependent approach may be useful for research purposes on the analysis of custom-made immunoassays using advanced optical imaging setups that includes a precise automated scanning stage and other opto-mechanical components, but it is not the right approach for hand-held, real-time rapid diagnostic tests.
Note that although the work here was focused on smartphone/wirelessly-enabled device-based and smartphone/wirelessly-enabled device-activated/managed RDT readers as the most advantageous architecture, many of the technologies described herein apply equally well to any reader architecture based on digital imaging.